Downregulation of Cholinergic Receptor Alpha 5 (CHRNA5) in MCF7 breast cancer cells

Cholinergic Receptor Nicotinic Alpha 5 (CHRNA5), an important susceptibility locus for nicotine addiction and lung cancer, is not well studied in breast cancer. In our study, CHRNA5 was transiently depleted in MCF7 cells and transcriptomic changes were compared to siRNA controls. We for the first time showed by microarray analysis that silencing of CHRNA5 in MCF7 breast cancer cells, downregulated genes involved in the cell cycle and proliferation while resulting in reduced cell viability, DNA synthesis and G1 growth arrest. In addition, simultaneous treatment of CHRNA5 siRNA and topoisomerase inhibitors showed an important role of CHRNA5 in increased drug sensitivity. Phalloidin stained CHRNA5 siRNA treated cells on the other hand exhibited a distinct cellular morphotype with increased cellular extensions and a transcriptome characterized by mixed expression of epithelial-mesenchymal genes. Through bioinformatics analysis of the public transcriptome data we demonstrated a strong positive association of expression signature of CHRNA5 RNAi with that of a differentiated cell as well as hormone starvation. Hence, our study implicates CHRNA5 as an antiproliferative differentiation marker in breast cancer.

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